The double isotope method for the measurement of energy expenditure and material balance is a noninvasive technique that uses safe, stable isotopic tracers. The method takes advantage of the phenomenon of complete mixing of the oxygen from water with the oxygen from carbon dioxide. Thus, the elimination rates of 2H and 180 from body water will differ as the former will be eliminated as water while the later will be eliminated both as water and as carbon dioxide. The difference in the elimination rates will be the carbon dioxide production rate, which is directly related to energy expenditure. The double isotope technique only requires the collection of periodic physiological fluid samples following the oral administration of doubly labelled water, and therefore eliminates the restrictive chambers used for direct calorimetry, and the restrictive gas collection apparatus used for continuous indirect calorimetry. The method has been extensively validated in small animals with an accuracy and precision of about 5%. However, despite its simplicity and potential, it has never been used in man, because of the high isotope costs required by the previously employed analytical techniques. We have reduced these costs through the use of high precision isotope ratio mass spectrometry. Our preliminary studies have demonstrated the feasibility in man, and we propose to further refine the method and to begin to employ it in the study of human metabolism. This proposal has three major goals. 1) The comparison of the double isotope method with the standard techniques including indirect calorimetry in adults and infants, and dietary record. These comparisons will be performed under steady state conditions, and under conditions of weight gain. 2) The identification of the limitations of the method, and minimization of the isotopic loadind dose through a careful investigation of the basic assumptions underlying the method. 3) Application of the double isotope method for the determination of the energy requirements of the elderly, the measurement of the metabolic response to hyperalimentation, and the measurement of energy balance in diabetic adolescents.